We will be evaluating the biological properties of 2 series of agents that may exhibit anti-nicotine activity. One series is analogs of nicotine and the other series are phenacyl derivatives. Some of these agents may exhibit "hemichonium-like" activity. We are especially interested in non-quaternary derivatives. As yet no effective non-quaternary hemicholinium compound has been discovered. We are exploring the SAR of aminotetralins and dopamine analogs for their ability to inhibit adrenergic nerve terminals and adrenergic ganglia. Some of these compounds also activate alpha and beta receptors. We have postulated that there is a dopamine activated mechanism that inhibits the release of norepinephrine from the adrenergic nerve terminals. Some of these compounds are effective at less than 1.0 microgram/kg. One of the aminotetralins, M-8, is a potent coronary vessel dilator. On intravenous infusion of 10 microgram/kg in the dog the total coronary flow increases 50-60%. The increase in flow is accompanied by a decrease in heart rate and a decrease in arterial pressure. BIBLIOGRAPHIC REFERENCES: Ilhan, M., Long, J.P. and Cannon, J.G. Effects of some dopamine analogs and haloperiodol on response to stimulation of adrenergic nerves using cat atria in vitro. Arch. int. Pharmacodyn. 219:193-204, 1976. Peterson, L.A., Sharabi, F.M., Long, J.P., Taylor, C.A. and Barfknecht, C.F. The antagonism of nicotine induced cardiovascular responses by DMAE and DEO analogs. Eur. J. Pharmacol. 37:303-310, 1976.